osteoprotegerin and Infertility--Female

To evaluate if the levels of the central regulators of osteoclast activity, osteoprotegerin (OPG) and receptor activator for nuclear factor kappaB-ligand (RANk-L), correlate with bone mineral density (BMD) parameters in premenopausal infertile women.. Cross-sectional study.. Academic infertility practice.. 82 Infertile, but otherwise healthy, premenopausal women< 42 years age presenting for routine care.. BMD assessment; serum samples (cycle days 1 to 3), questionnaire addressing demographics, medical, social, family, and personal histories.. BMD categorized as "Low" (Z -1.0); Biomarkers of bone metabolism (BAP, TRAP, NTX, OPG, RANK-L) and ovarian reserve (FSH, estradiol).. The prevalence of low BMD was 23% (19/82). Significantly lower levels of OPG were observed in association with low BMD compared with normal BMD (1.37 +/- 0.57 versus 2.0 +/- 1.05 pMol/L). Multivariable logistic regression analyses revealed low OPG levels as independent predictors of low BMD after adjusting for parameters known to influence bone density.. We demonstrate an independent relationship between low circulating levels of OPG and low BMD in premenopausal healthy, albeit infertile, women.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Alkaline Phosphatase; Biomarkers; Bone Density; Collagen Type I; Cross-Sectional Studies; Down-Regulation; Estradiol; Female; Follicle Stimulating Hormone, Human; Humans; Infertility, Female; Isoenzymes; Logistic Models; Osteoprotegerin; Peptides; Premenopause; RANK Ligand; Surveys and Questionnaires; Tartrate-Resistant Acid Phosphatase

Failure of apoptosis of refluxed endometrial cells within the peritoneal cavity is a possible etiologic factor for development of endometriosis. Osteoprotegerin (OPG) is a survival factor that exerts its effect by binding to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thus preventing TRAIL from binding to the apoptosis receptors DR4 and DR5. In the present study, we addressed the possibility that the TRAIL/OPG system is involved in the pathogenesis of endometriosis.. Concentrations of OPG and TRAIL in the peritoneal fluid (PF) of women with or without endometriosis were measured using specific enzyme-linked immunoabsorbent assay. The expression of DR4 and DR5 in the endometriotic tissue was examined by reverse transcription-polymerase chain reaction.. OPG concentrations in PF of women with endometriosis were significantly higher than those of women without endometriosis (P=0.006). With respect to the stages of the disease, the concentrations of OPG in women with stage III/IV endometriosis were significantly higher than in those without endometriosis and those with stage I/II endometriosis. On the other hand, the ratios of TRAIL/OPG concentrations were significantly lower in stage III/IV endometriosis compared to those in non-endometriosis and stage I/II endometriosis. DR5 mRNA expression was clearly detected in all the endometriotic tissues studied.. These findings suggest that the TRAIL/OPG system is involved in the pathophysiology of endometriosis, possibly affecting the apoptosis of endometriotic cells.

Topics: Adult; Apoptosis Regulatory Proteins; Ascitic Fluid; Case-Control Studies; Endometriosis; Female; Glycoproteins; Humans; Infertility, Female; Membrane Glycoproteins; Osmolar Concentration; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor; RNA, Messenger; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha